491 lines
No EOL
107 KiB
HTML
491 lines
No EOL
107 KiB
HTML
<?xml version="1.0" encoding="utf-8"?>
|
||
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
|
||
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">
|
||
|
||
<head><meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
|
||
<!-- AppResources meta begin -->
|
||
<meta name="paf-app-resources" content="" />
|
||
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
||
|
||
<!-- AppResources meta end -->
|
||
|
||
<!-- TemplateResources meta begin -->
|
||
<meta name="paf_template" content="" />
|
||
|
||
<!-- TemplateResources meta end -->
|
||
|
||
<!-- Logger begin -->
|
||
<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK47342" /><meta name="ncbi_domain" content="mlprobe" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK47342/" /><meta name="ncbi_pagename" content="Probe Report for NOX1 Inhibitors - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
||
<!-- Logger end -->
|
||
|
||
<title>Probe Report for NOX1 Inhibitors - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf</title>
|
||
|
||
<!-- AppResources external_resources begin -->
|
||
<link rel="stylesheet" href="/core/jig/1.15.2/css/jig.min.css" /><script type="text/javascript" src="/core/jig/1.15.2/js/jig.min.js"></script>
|
||
|
||
<!-- AppResources external_resources end -->
|
||
|
||
<!-- Page meta begin -->
|
||
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Probe Reports from the NIH Molecular Libraries Program [Internet]" /><meta name="citation_title" content="Probe Report for NOX1 Inhibitors" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2010/09/02" /><meta name="citation_author" content="SJ Brown" /><meta name="citation_author" content="D Gianni" /><meta name="citation_author" content="G Bokoch" /><meta name="citation_author" content="BA Mercer" /><meta name="citation_author" content="P Hodder" /><meta name="citation_author" content="HR Rosen" /><meta name="citation_pmid" content="21433358" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK47342/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Probe Report for NOX1 Inhibitors" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="SJ Brown" /><meta name="DC.Contributor" content="D Gianni" /><meta name="DC.Contributor" content="G Bokoch" /><meta name="DC.Contributor" content="BA Mercer" /><meta name="DC.Contributor" content="P Hodder" /><meta name="DC.Contributor" content="HR Rosen" /><meta name="DC.Date" content="2010/09/02" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK47342/" /><meta name="description" content="NADPH oxidase 1 (NOX1) is highly expressed in colon epithelial cells, where it generates reactive oxygen species (ROS) to interact with normal and pathogenic bacteria. Excessive reactive ROS production is associated with damage to the intestinal mucosa, particularly in mucosal lesions of inflammatory bowel disease (IBD). Studies have shown that NOX1 levels are increased in human prostate cancer, and might also play a role in angiogenesis, cell growth, and tumor pathogenesis. The identification of potent, selective inhibitors of NOX1 may lead to potential therapeutic candidates for excess cell proliferation, cancer, and IBD. This project demonstrated that the molecular probe ML090 (CID-616479) is neither a hydrogen peroxide scavenger, nor a general cell toxin on the time scale of cellular NOX inhibition assays. The specificity of the probe for NOX1 over NOX2, 3 and 4 in a 293 assay system suggests that a target specific to the NOX1 system is the molecular target. ML090 should serve as a useful probe for cellular systems where inhibition of NOX1, and not other members of the NOX family, is desired. This compound provides a significant improvement over the previously existing non-selective NOX inhibitor, diphenylene iodium." /><meta name="og:title" content="Probe Report for NOX1 Inhibitors" /><meta name="og:type" content="book" /><meta name="og:description" content="NADPH oxidase 1 (NOX1) is highly expressed in colon epithelial cells, where it generates reactive oxygen species (ROS) to interact with normal and pathogenic bacteria. Excessive reactive ROS production is associated with damage to the intestinal mucosa, particularly in mucosal lesions of inflammatory bowel disease (IBD). Studies have shown that NOX1 levels are increased in human prostate cancer, and might also play a role in angiogenesis, cell growth, and tumor pathogenesis. The identification of potent, selective inhibitors of NOX1 may lead to potential therapeutic candidates for excess cell proliferation, cancer, and IBD. This project demonstrated that the molecular probe ML090 (CID-616479) is neither a hydrogen peroxide scavenger, nor a general cell toxin on the time scale of cellular NOX inhibition assays. The specificity of the probe for NOX1 over NOX2, 3 and 4 in a 293 assay system suggests that a target specific to the NOX1 system is the molecular target. ML090 should serve as a useful probe for cellular systems where inhibition of NOX1, and not other members of the NOX family, is desired. This compound provides a significant improvement over the previously existing non-selective NOX inhibitor, diphenylene iodium." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK47342/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/mlprobe/ml090/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK47342/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
|
||
|
||
<!-- Page meta end -->
|
||
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico" /><meta name="ncbi_phid" content="CE8D12EF7D6690A1000000000022001F.m_13" />
|
||
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3985586/3808861/4121862/3974050/3917732/251717/4216701/14534/45193/4113719/3849091/3984811/3751656/4033350/3840896/3577051/3852958/4008682/4207974/4206132/4062871/12930/3964959/3854974/36029/4128070/9685/3549676/3609192/3609193/3609213/3395586.css" /><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3411343/3882866.css" media="print" /></head>
|
||
<body class="book-part">
|
||
<div class="grid">
|
||
<div class="col twelve_col nomargin shadow">
|
||
<!-- System messages like service outage or JS required; this is handled by the TemplateResources portlet -->
|
||
<div class="sysmessages">
|
||
<noscript>
|
||
<p class="nojs">
|
||
<strong>Warning:</strong>
|
||
The NCBI web site requires JavaScript to function.
|
||
<a href="/guide/browsers/#enablejs" title="Learn how to enable JavaScript" target="_blank">more...</a>
|
||
</p>
|
||
</noscript>
|
||
</div>
|
||
<!--/.sysmessage-->
|
||
<div class="wrap">
|
||
<div class="page">
|
||
<div class="top">
|
||
<div id="universal_header">
|
||
<section class="usa-banner">
|
||
<div class="usa-accordion">
|
||
<header class="usa-banner-header">
|
||
<div class="usa-grid usa-banner-inner">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" />
|
||
<p>An official website of the United States government</p>
|
||
<button class="non-usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" type="button">
|
||
<span class="usa-banner-button-text">Here's how you know</span>
|
||
</button>
|
||
</div>
|
||
</header>
|
||
<div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" aria-hidden="true">
|
||
<div class="usa-banner-guidance-gov usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The .gov means it's official.</strong>
|
||
<br />
|
||
Federal government websites often end in .gov or .mil. Before
|
||
sharing sensitive information, make sure you're on a federal
|
||
government site.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
<div class="usa-banner-guidance-ssl usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The site is secure.</strong>
|
||
<br />
|
||
The <strong>https://</strong> ensures that you are connecting to the
|
||
official website and that any information you provide is encrypted
|
||
and transmitted securely.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<div class="usa-overlay"></div>
|
||
<header class="ncbi-header" role="banner" data-section="Header">
|
||
|
||
<div class="usa-grid">
|
||
<div class="usa-width-one-whole">
|
||
|
||
<div class="ncbi-header__logo">
|
||
<a href="/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" />
|
||
</a>
|
||
</div>
|
||
|
||
<div class="ncbi-header__account">
|
||
<a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a>
|
||
<button id="account_info" class="header-button" style="display:none" aria-controls="account_popup" type="button">
|
||
<span class="fa fa-user" aria-hidden="true">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" width="20px" height="20px">
|
||
<g style="fill: #fff">
|
||
<ellipse cx="12" cy="8" rx="5" ry="6"></ellipse>
|
||
<path d="M21.8,19.1c-0.9-1.8-2.6-3.3-4.8-4.2c-0.6-0.2-1.3-0.2-1.8,0.1c-1,0.6-2,0.9-3.2,0.9s-2.2-0.3-3.2-0.9 C8.3,14.8,7.6,14.7,7,15c-2.2,0.9-3.9,2.4-4.8,4.2C1.5,20.5,2.6,22,4.1,22h15.8C21.4,22,22.5,20.5,21.8,19.1z"></path>
|
||
</g>
|
||
</svg>
|
||
</span>
|
||
<span class="username desktop-only" aria-hidden="true" id="uname_short"></span>
|
||
<span class="sr-only">Show account info</span>
|
||
</button>
|
||
</div>
|
||
|
||
<div class="ncbi-popup-anchor">
|
||
<div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true">
|
||
<div class="ncbi-popup-head">
|
||
<button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu" type="button">
|
||
<span class="fa fa-times">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 48 48" width="24px" height="24px">
|
||
<path d="M38 12.83l-2.83-2.83-11.17 11.17-11.17-11.17-2.83 2.83 11.17 11.17-11.17 11.17 2.83 2.83 11.17-11.17 11.17 11.17 2.83-2.83-11.17-11.17z"></path>
|
||
</svg>
|
||
</span>
|
||
<span class="usa-sr-only">Close</span></button>
|
||
<h4>Account</h4>
|
||
</div>
|
||
<div class="account-user-info">
|
||
Logged in as:<br />
|
||
<b><span class="username" id="uname_long">username</span></b>
|
||
</div>
|
||
<div class="account-links">
|
||
<ul class="usa-unstyled-list">
|
||
<li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li>
|
||
<li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li>
|
||
<li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li>
|
||
<li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</header>
|
||
<div role="navigation" aria-label="access keys">
|
||
<a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a>
|
||
<a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a>
|
||
<a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a>
|
||
<a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a>
|
||
<a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a>
|
||
</div>
|
||
<section data-section="Alerts">
|
||
<div class="ncbi-alerts-placeholder"></div>
|
||
</section>
|
||
</div>
|
||
<div class="header">
|
||
<div class="res_logo"><h1 class="res_name"><a href="/books/" title="Bookshelf home">Bookshelf</a></h1><h2 class="res_tagline"></h2></div>
|
||
<div class="search"><form method="get" action="/books/"><div class="search_form"><label for="database" class="offscreen_noflow">Search database</label><select id="database"><optgroup label="Recent"><option value="books" selected="selected" data-ac_dict="bookshelf-search">Books</option><option value="pubmed">PubMed</option><option value="clinvar">ClinVar</option><option value="refseq" class="last">RefSeq</option></optgroup><optgroup label="All"><option value="gquery">All Databases</option><option value="assembly">Assembly</option><option value="biocollections">Biocollections</option><option value="bioproject">BioProject</option><option value="biosample">BioSample</option><option value="books" data-ac_dict="bookshelf-search">Books</option><option value="clinvar">ClinVar</option><option value="cdd">Conserved Domains</option><option value="gap">dbGaP</option><option value="dbvar">dbVar</option><option value="gene">Gene</option><option value="genome">Genome</option><option value="gds">GEO DataSets</option><option value="geoprofiles">GEO Profiles</option><option value="gtr">GTR</option><option value="ipg">Identical Protein Groups</option><option value="medgen">MedGen</option><option value="mesh">MeSH</option><option value="nlmcatalog">NLM Catalog</option><option value="nuccore">Nucleotide</option><option value="omim">OMIM</option><option value="pmc">PMC</option><option value="protein">Protein</option><option value="proteinclusters">Protein Clusters</option><option value="protfam">Protein Family Models</option><option value="pcassay">PubChem BioAssay</option><option value="pccompound">PubChem Compound</option><option value="pcsubstance">PubChem Substance</option><option value="pubmed">PubMed</option><option value="snp">SNP</option><option value="sra">SRA</option><option value="structure">Structure</option><option value="taxonomy">Taxonomy</option><option value="toolkit">ToolKit</option><option value="toolkitall">ToolKitAll</option><option value="toolkitbookgh">ToolKitBookgh</option></optgroup></select><div class="nowrap"><label for="term" class="offscreen_noflow" accesskey="/">Search term</label><div class="nowrap"><input type="text" name="term" id="term" title="Search Books. Use up and down arrows to choose an item from the autocomplete." value="" class="jig-ncbiclearbutton jig-ncbiautocomplete" data-jigconfig="dictionary:'bookshelf-search',disableUrl:'NcbiSearchBarAutoComplCtrl'" autocomplete="off" data-sbconfig="ds:'no',pjs:'no',afs:'no'" /></div><button id="search" type="submit" class="button_search nowrap" cmd="go">Search</button></div></div></form><ul class="searchlinks inline_list"><li>
|
||
<a href="/books/browse/">Browse Titles</a>
|
||
</li><li>
|
||
<a href="/books/advanced/">Advanced</a>
|
||
</li><li class="help">
|
||
<a href="/books/NBK3833/">Help</a>
|
||
</li><li class="disclaimer">
|
||
<a target="_blank" data-ga-category="literature_resources" data-ga-action="link_click" data-ga-label="disclaimer_link" href="https://www.ncbi.nlm.nih.gov/books/about/disclaimer/">Disclaimer</a>
|
||
</li></ul></div>
|
||
</div>
|
||
|
||
|
||
|
||
<!--<component id="Page" label="headcontent"/>-->
|
||
|
||
</div>
|
||
<div class="content">
|
||
<!-- site messages -->
|
||
<!-- Custom content 1 -->
|
||
<div class="col1">
|
||
|
||
</div>
|
||
|
||
<div class="container">
|
||
<div id="maincontent" class="content eight_col col">
|
||
<!-- Custom content in the left column above book nav -->
|
||
<div class="col2">
|
||
|
||
</div>
|
||
|
||
<!-- Book content -->
|
||
|
||
|
||
<!-- Custom content between navigation and content -->
|
||
<div class="col3">
|
||
|
||
</div>
|
||
|
||
<div class="document">
|
||
<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/mlprobe/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" alt="Cover of Probe Reports from the NIH Molecular Libraries Program" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Probe Reports from the NIH Molecular Libraries Program [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK47342_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK47342_dtls__"><div>Bethesda (MD): National Center for Biotechnology Information (US); 2010-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/mlprobe/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml095/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml089/" title="Next page in this title">Next ></a></div></div></div></div></div>
|
||
<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK47342_"><span class="title" itemprop="name">Probe Report for NOX1 Inhibitors</span></h1><p class="contrib-group"><span itemprop="author">SJ Brown</span>, <span itemprop="author">D Gianni</span>, <span itemprop="author">G Bokoch</span>, <span itemprop="author">BA Mercer</span>, <span itemprop="author">P Hodder</span>, and <span itemprop="author">HR Rosen</span>.</p><p class="small">Received: <span itemprop="datePublished">April 23, 2009</span>; Last Update: <span itemprop="dateModified">September 2, 2010</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p>NADPH oxidase 1 (NOX1) is highly expressed in colon epithelial cells, where it generates reactive oxygen species (ROS) to interact with normal and pathogenic bacteria. Excessive reactive ROS production is associated with damage to the intestinal mucosa, particularly in mucosal lesions of inflammatory bowel disease (IBD). Studies have shown that NOX1 levels are increased in human prostate cancer, and might also play a role in angiogenesis, cell growth, and tumor pathogenesis. The identification of potent, selective inhibitors of NOX1 may lead to potential therapeutic candidates for excess cell proliferation, cancer, and IBD. This project demonstrated that the molecular probe ML090 (CID-616479) is neither a hydrogen peroxide scavenger, nor a general cell toxin on the time scale of cellular NOX inhibition assays. The specificity of the probe for NOX1 over NOX2, 3 and 4 in a 293 assay system suggests that a target specific to the NOX1 system is the molecular target. ML090 should serve as a useful probe for cellular systems where inhibition of NOX1, and not other members of the NOX family, is desired. This compound provides a significant improvement over the previously existing non-selective NOX inhibitor, diphenylene iodium. </p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> 1 R03 MH083264-01A1</p><p><b>Screening Center Name & PI:</b> Scripps Research Institute Molecular Screening Center, H. Rosen, P. Hodder</p><p><b>Chemistry Center Name & PI:</b> Scripps Research Institute Molecular Screening Center, Scripps Research Institute Molecular Screening Center, H. Rosen, W. Roush</p><p><b>Assay Submitter & Institution:</b> Gary Bokoch, TSRI</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></p><div id="ml090.s2"><h2 id="_ml090_s2_">Probe Structure & Characteristics</h2><p>CID-616479, 5,11-Dihydroquinoxalino[2,3-b]quinoxaline, has been tested in 10 primary screening assays reported in Pubchem and is reported inactive in all of these. In this report, we describe a series of experiments that demonstrate that CID-616479 selectively inhibits NOX1 and is a significant improvement over diphenyl iodium—the existing, nonselective NOX inhibitor.</p><div id="ml090.fu1" class="figure"><div class="graphic"><img src="/books/NBK47342/bin/ml090fu1.jpg" alt="Image ml090fu1" /></div></div><p><b>NOX1 Inhibitor Probe</b></p><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/26535836" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-26535836</a></b></p><p><b>CID-616479</b></p><p><b><a href="/pcsubstance/?term=ML090[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML090</a></b></p><div id="ml090.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml090.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID/ML</th><th id="hd_h_ml090.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">SID</th><th id="hd_h_ml090.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Target Name</th><th id="hd_h_ml090.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Target IC<sub>50</sub> micromolar</th><th id="hd_h_ml090.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Anti-targets</th><th id="hd_h_ml090.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Anti-target IC<sub>50</sub></th><th id="hd_h_ml090.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Selectivity</th><th id="hd_h_ml090.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Secondary Assay: 293-NOX1 IC<sub>50</sub> [AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml090.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID-616479/<a href="/pcsubstance/?term=ML090[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML090</a></td><td headers="hd_h_ml090.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/26535836" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-26535836</a></td><td headers="hd_h_ml090.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1</td><td headers="hd_h_ml090.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.09</td><td headers="hd_h_ml090.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX2, NOX3, and NOX4</td><td headers="hd_h_ml090.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>10 μM</td><td headers="hd_h_ml090.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>100</td><td headers="hd_h_ml090.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.36 micromolar</td></tr></tbody></table></div></div></div><div id="ml090.s3"><h2 id="_ml090_s3_">Recommendations for the scientific use of this probe</h2><p>This compound is useful for cell-based assays in which it is desirable to specifically block NOX1 activity, including models of cancer cell proliferation and inflammation. Inhibition of NOX blocks reactive oxygen species generation. The current probe, diphenylene iodium, is widely used in research, for example there are 293 references found on searching Pubmed for “DPI and ROS”. This probe is the first selective inhibitor of NOX1 and provides a significant improvement over the widely used, nonspecific compound diphenylene iodium.</p></div><div id="ml090.s4"><h2 id="_ml090_s4_">1. Scientific Rationale for Project</h2><p>Host defense mechanisms are diverse and include receptor-initiated signaling pathways, antibody and cytokine production, and the generation of reactive oxygen species (ROS) such as hydroxyl radical and hypochlorus acid to kill microorganisms (<a class="bk_pop" href="#ml090.r1">1</a>). In activated phagocytic cells, the membrane integrated protein gp91<sup>phox</sup> serves as the catalytic cytochrome b subunit of the respiratory burst oxidase used to generate superoxide in an NADPH-dependent manner for host defense (<a class="bk_pop" href="#ml090.r2">2</a>). Generation of ROS has also been identified in non-phagocytic cells (<a class="bk_pop" href="#ml090.r3">3</a>). One important enzyme involved in ROS production in non-leukocyte tissues is <b>NADPH oxidase 1 (NOX1)</b>, a homolog of gp91<sup>phox</sup>. NOX1 is highly expressed in colon epithelial cells where it can generate ROS to interact with normal and pathogenic bacteria (<a class="bk_pop" href="#ml090.r3" data-bk-pop-others="ml090.r4 ml090.r5">3–5</a>). However, excess ROS production is associated with damage to the intestinal mucosa, particularly in mucosal lesions of inflammatory bowel disease (IBD) (<a class="bk_pop" href="#ml090.r4">4</a>). Studies showing that NOX1 levels are increased in human prostate cancer (<a class="bk_pop" href="#ml090.r6">6</a>) and that cells overexpressing NOX1 have a transformed appearance, exhibit anchorage-independent growth, and induce vascularized tumor formation in athymic mice (<a class="bk_pop" href="#ml090.r3">3</a>, <a class="bk_pop" href="#ml090.r7">7</a>), suggest that NOX1 may also play a role in angiogenesis, cell growth, and tumor pathogenesis (<a class="bk_pop" href="#ml090.r8">8</a>, <a class="bk_pop" href="#ml090.r9">9</a>). The identification of potent, selective inhibitors of NOX1 may lead to potential candidates for excess cell proliferation, cancer, and IBD. The known NOX inhibitors are of low micromolar potencies and are non-selective(<a class="bk_pop" href="#ml090.r10">10</a>).</p></div><div id="ml090.s5"><h2 id="_ml090_s5_">2. Project Description</h2><div id="ml090.s6"><h3>a. The main goal of this project is to find cell based -selective inhibitors of NOX1.</h3><p>The following goals were listed in the CPDP:</p><ol><li class="half_rhythm"><div>Probes should not induce cell death (page 29, R03 application).</div></li><li class="half_rhythm"><div>Probes should exhibit saturable inhibitor activity (page 29).</div></li><li class="half_rhythm"><div>Probes should exhibit inhibitory activity against NOX-1 selectively (page 29), or against other NOX proteins in general (page 32);</div></li><li class="half_rhythm"><div>Probes should block the NOX1-derived ROS-dependent production of pro-inflammatory cytokines (page 38).</div></li></ol></div><div id="ml090.s7"><h3>b. Assay implementation and screening</h3><div id="ml090.s8"><h4>i. PubChem Bioassay Name(s), AID(s) Assay-Type (Primary, DR Counterscreen, Secondary)</h4><div id="ml090.t2" class="table"><h3><span class="label">Table 2</span><span class="title">PubChem BioAssays</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Brief Name</th><th id="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Name</th><th id="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Type</th><th id="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target</th><th id="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Powder Sample</th><th id="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound Concentration</th></tr></thead><tbody><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Maybridge 16K library: primary screen <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1792" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1792</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary cellular high-throughput screening assay to measure NOX1 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary Assay (1X% INH)</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Maybridge 16K library: counterscreen screen Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary biochemical high-throughput screening assay to measure H202- luminol inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary Assay (1X% INH)</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H2O2</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Maybridge 16K Confirmation screen Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmation cellular high- throughput screening assay to measure NOX1 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmation Assay (triplicate) Counterscreen</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7 and 3.3 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cytoxicity Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cellular Cytotoxicity</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay (triplicate) Confirmation</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cellular ATP</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1 293 confirmation Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmation screening cellular assay to measure NOX 1 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay (3X% INH)</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1 293 dose response Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dose response cellular assay to measure NOX 1 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dose Response Assay</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-point, 1:4 dilution starting at 33 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX2 293 counterscreen Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreening cellular assay to measure NOX 2 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cell-based Low Throughput Assay</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX2</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX 3 293 counterscreen Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreening cellular assay to measure NOX 3 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cell-based Low Throughput Assay</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX3</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX 4 293 Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreening cellular assay to measure NOX 4 inhibition</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cell-based Low Throughput Assay</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX4</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 μM</td></tr><tr><td headers="hd_h_ml090.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Xanthine Oxidase Summary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreen for inhibitors of Xanthine Oxidase</td><td headers="hd_h_ml090.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical Assay</td><td headers="hd_h_ml090.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Xanthine Oxidase</td><td headers="hd_h_ml090.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml090.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dose response</td></tr></tbody></table></div></div></div><div id="ml090.s9"><h4>ii. Assay Rationale and Description</h4><div id="ml090.t3" class="table"><h3><span class="label">Table 3</span><span class="title">Assay Rationale and Description</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.t3_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">AID</th><th id="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay Rationale</th><th id="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assay Description</th><th id="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Z′</th><th id="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">S:B</th></tr></thead><tbody><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1 HT29 Primary HTS- MaybridgeLibrary <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1792" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1792</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to measure the ability of compounds to inhibit NOX1 activity.</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This cell-based assay utilizes a luminol chemiluminescence assay to monitor intracellular reactive oxygen species (ROS) in the transformed colonic epithelial cell line HT29. In this assay, cells are incubated with compounds for 1 hour, and then luminol, and horseradish peroxidase (HRP) are added. Interaction between the luminol and cell-generated ROS yields an unstable endoperoxide and emission of photons that can be detected by a luminometer. As designed, compounds that inhibit NOX1 activity will reduce cellular ROS production, leading to reduced probe-ROS interactions and reduced well luminescence. Compounds were tested in singlicate at a concentration of 7 μM.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.48 ± 0.08</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">18.5 ± 4.4</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Maybridge 16K library: counterscreen screen <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1823" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1823</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay to eliminate H202 scavenger compounds that would behave as false positives in the primary screening assay</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This cell-free assay utilizes a luminol probe-based chemiluminescence assay. In this assay, hydrogen peroxide and test compound are incubated for 1 hour and then luminol and horseradish peroxidase (HRP) are added. Interaction between the luminol and ROS yields an unstable endoperoxide and emission of photons that can be detected by a luminometer. As designed, compounds that scavenge hydrogen peroxide will reduce well luminescence. Compounds were tested in singlicate at a concentration of 7 μM.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.9</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">30</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cytotoxicity Assay (Please see <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a>)</td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay to eliminate cytotoxic compounds that would behave as false positives in the primary screening assay</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">In this assay, cells were incubated for 1 hour with test compound. Cell viability was measure with the Cell Titre Glo reagent that measures cellular ATP.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1 HT29 confirmation <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to confirm the ability of compounds to inhibit NOX1 activity.</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Same as the Primary screen except that the compounds were tested in triplicate at 6.7 and 2.2 micromolar</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX 1-HEK confirmatory assays <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to confirm the ability of compounds to inhibit NOX1 activity in the NOX1 -293 transfection format</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prior to the transfection, 90% confluent 293 cells are seeded into 6-well plates and incubated overnight. The NOX1 components pRK5-Myc-NOX1, -NOXO1, and -NOXA1and were cotransfected with pRK5-myc-Rac1CA- Q61L the 293 cells in 6 well plates. A total of two micrograms total DNA, combined with four microliters lipofectamine and 100 ul OptiMem was added per well. After 16 hours the media was removed and replaced with 2 ml fresh media containing either the test or control compounds or vehicle control. Following 2 hours treatment at 37 degrees Celsius the cells were trypsinized and the cells from each well were resuspended into 1 mL HBSS. Sixty microliters of the cell suspension was dispensed in wells of a 96 well plate and 60 microliters of HBSS was added assay followed by 80 microlitres of a mixture of luminol and HRP. Chemiluminescence was measured for 30 minutes. Compounds were tested in singlicate at a concentration of 100 μM.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX 1 HEK DR confirmation assay <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to determine the potency of compounds to inhibit NOX1 activity in the NOX -293 transfection format.</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This assay is the same as the NOX1-HEK confirmatory except that the cells were treated with a 10 point dose response of test compound.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX -2, -3 and -4 HEK selectivity assays <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to evaluate the ability of compounds to inhibit NOX-2, -3 or -4 activity in the NOX -293 transfection format</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">In these selectivity assays the cells are prepared in the same manner as the NOX1-HEK transfection assay except that the cells are transfected with the appropriate expression vectors for each NOX subtype. NOX2: pRK5-Myc- NOX2, pRK5-p67phox, pRK5-p47phox and pRK5-myc-Rac1CA-Q61L. NOX-3: pRK5-Myc-NOX3, pRK5-NOXO1, pRK5-NOXA1and pRK5- myc-Rac1CA-Q61L. NOX-4: pRK5-Myc-NOX4 and pRK5-p22phox. NOX activity was determined by chemiluninescence as for the NOX1 293 assay. Compounds were tested in tripicate at a concentration of 10 μM.</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml090.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Xanthine Oxidase <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1796</a></td><td headers="hd_h_ml090.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The purpose of this assay is to evaluate the ability of compounds to inhibit ROS production by another cellular sources such as xanthine oxidase</td><td headers="hd_h_ml090.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">In this assay, 50 microliters of a solution of 0.25 U/ml of xanthine oxidase in HBSS (0.5 mg/mL) was dispensed to all wells of a 96 well plate followed by 1 microliters of 1 mM DPI, DMSO or test compounds. The plates were incubated for 5 minutes at room temperature and then 50 microliters of 2 mM hypoxanthine was dispensed to all wells followed by 80 microliters of HRP/luminol mix and reading luminesence</td><td headers="hd_h_ml090.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml090.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="ml090.tfn2"><p class="no_margin">NA, Not Applicable</p></div></dd></dl></div></div></div><div id="ml090.t4" class="table"><h3><span class="label">Table 4</span><span class="title">Reagents and Source</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.t4_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay</th><th id="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Reagent (Source)</th></tr></thead><tbody><tr><td headers="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primary and confirmation screens</td><td headers="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HT29 cells (ATCC, part HTB-38)<br /> DPI (Sigma, part D2926-10mg)<br /> Luminol (Sigma, part 09253-5g)<br /> HRP (EMD Bioscience, part 516531-5KU).<br /> HBSS(Invitrogen, part 14025-092)<br />384-well plates (Corning, part 3704)</td></tr><tr><td headers="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hydrogen peroxide scavenger Counterscreen</td><td headers="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Same as above, except that HT29 cells and DPI are not used and Hydrogen Peroxide (Sigma, part 216763)<br /> N-acetyl cysteine (EMD, part 106425)</td></tr><tr><td headers="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cytotoxicity Assay</td><td headers="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HT29 cells (ATCC, part HTB-38)<br /> DPI (Sigma, part D2926-10mg)<br /> Cell Titre Glo (Promega, part G7572)<br /> Rotenone (Sigma Part</td></tr><tr><td headers="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NOX 1-4 HEK selectivity assays</td><td headers="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">293 cells (ATCC, part CRL-1573)<br />DPI (Sigma, part D2926-10mg)<br />Luminol (Sigma, part 09253-5g)<br />HRP (EMD Bioscience, part 516531-5KU).<br />Lipofectamine 2000 (Invitrogen 11688-019)<br />HBSS (Invitrogen, part 14025-092<br />OptiMem (Invitrogen, part 31985)<br />pRK5-Myc-NOX1 (Bokoch Lab)<br />pRK5-Myc-NOX2 (Bokoch Lab)<br />pRK5-NOXO1 (Bokoch Lab)<br />pRK5-NOXA1 (Bokoch Lab)<br />pRK5-myc-Rac1CA-Q61L (Bokoch Lab)<br /> pRK5-p67phox(Bokoch Lab)<br /> pRK5-p47phox(Bokoch Lab)<br /> pRK5-p22phox(Bokoch Lab)<br />6-well plates (Corning, part 3516)<br />96 well plates (Corning part Add Number</td></tr><tr><td headers="hd_h_ml090.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Xanthine Oxidase Counterscreen</td><td headers="hd_h_ml090.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Xanthine oxidase (Sigma, part X4376)<br /> Hypoxanthine (Sigma, part H9377)</td></tr></tbody></table></div></div></div><div id="ml090.s10"><h4>iii. Summary of Results</h4><p>Analysis of the NOX1 primary screening campaign identified 131 hits from NOX1-primary screen. The
|
||
full deck cell-free H2O2-based counterscreen assay eliminated 31 compounds because they demonstrated
|
||
significant H2O2 scavenger activity. The available hit compounds (96) were cherry picked and run in
|
||
the cell based confirmation assay for NOX1 activity. The compounds were tested in triplicate at 6.7
|
||
and 2.2 micromolar. These same cherry picked hits were then tested for cellular toxicity. None
|
||
showed significant cellular toxicity after 1 hr of incubation, the same incubation time as for the
|
||
primary and confirmatory assays. The results of the confirmatory assay were rank ordered and 44
|
||
compounds were selected and obtained as powders. The remaining experiments were conducted with these
|
||
samples. The repurchased compounds were tested for their ability to inhibit ROS production in 293
|
||
cells transfected with all NOX1 components at 100 micromolar concentration. In this assay, only 11
|
||
compounds out of 44 tested were able to significantly block ROS generation. These 11 compounds were
|
||
tested in dose-response starting at 33 micromolar in the NOX1-293 system. Only 7 compounds were able to significantly block ROS generation at this concentration. These 7 compounds were tested for their ability to block ROS generation by other NOX family members (NOX2, NOX3 and NOX4) in the 293 transfection system. The 7 compounds active in the 293 NOX1 system were also tested for their ability to block ROS generation mediated by xanthine oxidase, another cellular source of ROS. The most potent NOX1 inhibitor (in the 293 transfection assay) also demonstrated remarkable selectivity for NOX 1 over NOX2, 3 and 4. The data from the selectivity assays for CID-616479 are shown in the <a class="figpopup" href="/books/NBK47342/table/ml090.t5/?report=objectonly" target="object" rid-figpopup="figml090t5" rid-ob="figobml090t5">Summary Table</a> below. CID-616479 represents an improvement over known NOX1 inhibitors (e.g. DPI) because of its selectivity for NOX1 over NOX2, NOX3 and NOX4.</p></div></div><div id="ml090.s11"><h3>c. Probe Optimization</h3><div id="ml090.s12"><h4>i. SAR and Chemistry Strategy that led to the probe</h4><p>The probe molecule is a primary screening hit.</p></div></div></div><div id="ml090.s13"><h2 id="_ml090_s13_">3. Probe</h2><div id="ml090.s14"><h3>a. Chemical name</h3><p>6,11-dihydroquinoxalino[2,3-b]quinoxaline [<a href="/pcsubstance/?term=ML090[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML090</a>]</p></div><div id="ml090.s15"><h3>b. Chemical structure</h3><div id="ml090.fu2" class="figure"><div class="graphic"><img src="/books/NBK47342/bin/ml090fu2.jpg" alt="Image ml090fu2" /></div></div></div><div id="ml090.s16"><h3>c. Structural Verification Information of probe SID</h3><p>Maybridge states that the purity is greater than 90%. An LC-MS consistent with this purity was run on an aliquot of the sample for the MLSMR.</p></div><div id="ml090.s17"><h3>d. PubChem CID (corresponding to the SID)</h3><p>CID-616479</p></div><div id="ml090.s18"><h3>e. Available from a vendor</h3><p>Maybridge, part JFD 00196</p></div><div id="ml090.s19"><h3>f. Mode of action for biological activity</h3><p>The generation of reactive oxygen species (ROS) by NOX enzymes requires multiple protein components. We have shown that the probe molecule is not a hydrogen peroxide scavenger, nor is a general cell toxin on the time scale of the cellular NOX inhibition assays. The specificity of the probe for NOX1 over NOX2, 3 and 4 in the 293 assay system suggest that a target specific to the NOX1 system is the molecular target. CID-616479 should be a useful probe of cellular systems where inhibition of NOX1 and not NOX 2, NOX3 or NOX4 is desired.</p></div><div id="ml090.s20"><h3>g. Detailed synthetic pathway for making probe</h3><p>Not applicable, the probe is commercially available.</p></div><div id="ml090.s21"><h3>h. Summary of probe properties</h3><p>Aqueous solubility, -3.42750688310091; ADMET BBB, 0.21; ADMET BBB level, 1; ADMET absorption level, 0; ADMET solubility, -5.215; ADMET solubility level, 2</p></div><div id="ml090.s22"><h3>i. Summary of known probe properties</h3><div id="ml090.t5" class="table"><h3><span class="label">Table 5</span><span class="title">Probe Properties</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.t5_lrgtbl__"><table class="no_margin"><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>PubChem CID</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>CID-616479</b></td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>PubChem SID</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/26535836" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-26535836</a></b></td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>IUPAC Name</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6,11-dihydroquinoxalino[2,3-b]quinoxaline</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>MLS</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>002345386</b></td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>MF</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">C<sub>14</sub>H<sub>10</sub>N<sub>4</sub></td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>MW</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">234.256</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Formal Charge</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>H Acceptor</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>H Donor</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Atom Count</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Rotatable Bonds</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Rings</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Stereoatoms</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>AlogP</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.642</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>logD</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.642</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Polar surface area</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">49.84</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Aqueous solubility</b><sup><a class="bk_pop" href="#ml090.tfn3">a</a></sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−3.42750688310091</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>ADMET BBB</b><sup><a class="bk_pop" href="#ml090.tfn4">b</a></sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.21</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>ADMET BBB level</b><sup><a class="bk_pop" href="#ml090.tfn5">c</a></sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>ADMET absorption level</b><sup><a class="bk_pop" href="#ml090.tfn6">d</a></sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>ADMET solubility</b><sup><a class="bk_pop" href="#ml090.tfn7">e</a></sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−5.215</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>ADMET solubility level</b><sup>f</sup></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Vendor</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Maybridge</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Vendor Catalog Number</b></td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">JFD 00196</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>a</dt><dd><div id="ml090.tfn3"><p class="no_margin">Aqueous solubility is expressed as logS, where S is solubility in mol/L. The method used is the
|
||
multiple linear regression model based on Electrotopological State indices published in (<a class="bk_pop" href="#ml090.r11">11</a>, <a class="bk_pop" href="#ml090.r12">12</a>).</p></div></dd><dt>b</dt><dd><div id="ml090.tfn4"><p class="no_margin">ADMET_BBB: Log of Brain/Blood partition coefficient (LogBB). See (<a class="bk_pop" href="#ml090.r13">13</a>) for details on this method.</p></div></dd><dt>c</dt><dd><div id="ml090.tfn5"><p class="no_margin">ADMET_BBB_Level: Ranking of the LogBB values into one of the following levels (see (<a class="bk_pop" href="#ml090.r13">13</a>, <a class="bk_pop" href="#ml090.r14">14</a>) for details): 0: Very High 1: High 2: Medium 3: Low 4: Undefined (molecule is outside the confidence area of the regression model).</p></div></dd><dt>d</dt><dd><div id="ml090.tfn6"><p class="no_margin">ADMET Passive Intestinal Absorption properties. A ranking of the molecule into one of the
|
||
following levels (see (<a class="bk_pop" href="#ml090.r13">13</a>, <a class="bk_pop" href="#ml090.r14">14</a>) for details): 0: Good 1: Moderate 2: Poor 3: Very Poor</p></div></dd><dt>e</dt><dd><div id="ml090.tfn7"><p class="no_margin">ADMET_Solubility: Log of the water solubility at 25 degrees, LogSw, in mol/L. See (<a class="bk_pop" href="#ml090.r11">11</a>) for more information.</p></div></dd></dl></div></div></div></div></div><div id="ml090.s23"><h2 id="_ml090_s23_">4. Appendices</h2><div id="ml090.s24"><h3>a. Comparative data on (1) probes, (2) similar compound structures (establishing SAR) and (3) prior probes</h3><div id="ml090.t6" class="table"><h3><span class="label">Table 6</span><span class="title">Summary</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47342/table/ml090.t6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml090.t6_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml090.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound ID</th><th id="hd_h_ml090.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1 IC50 (μM) HT29</th><th id="hd_h_ml090.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX1-293 IC50 (μM)</th><th id="hd_h_ml090.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX2-293 %INH at 10 μM</th><th id="hd_h_ml090.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX3-293 %INH at 10 μM</th><th id="hd_h_ml090.t6_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NOX4-293 %INH at 10 μM</th><th id="hd_h_ml090.t6_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Xanthine Oxidase</th></tr></thead><tbody><tr><td headers="hd_h_ml090.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID-3101 Diphenylene iodium (DPI)</td><td headers="hd_h_ml090.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.17</td><td headers="hd_h_ml090.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N.D. (100% inhibition at 10 μM)</td><td headers="hd_h_ml090.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100</td><td headers="hd_h_ml090.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100</td><td headers="hd_h_ml090.t6_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100</td><td headers="hd_h_ml090.t6_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N.D.<sup><a class="bk_pop" href="#ml090.tfn9">1</a></sup></td></tr><tr><td headers="hd_h_ml090.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-616479</td><td headers="hd_h_ml090.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.09</td><td headers="hd_h_ml090.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.36</td><td headers="hd_h_ml090.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.2</td><td headers="hd_h_ml090.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−23</td><td headers="hd_h_ml090.t6_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−23</td><td headers="hd_h_ml090.t6_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.6</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="ml090.tfn8"><p class="no_margin">N.D. Not determined.</p></div></dd><dt>1</dt><dd><div id="ml090.tfn9"><p class="no_margin">The IC50 is reported in the literature to be in the low micromolar range (<a class="bk_pop" href="#ml090.r15">15</a>).</p></div></dd></dl></div></div></div></div></div><div id="ml090.s25"><h2 id="_ml090_s25_">5. Bibliography</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="ml090.r1">Takeya R, Sumimoto H. Molecular mechanism for activation of superoxide-producing NADPH oxidases. <span><span class="ref-journal">Mol Cells. </span>2003;<span class="ref-vol">16</span>:271–277.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14744014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14744014</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="ml090.r2">Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. <span><span class="ref-journal">Gene. </span>2001;<span class="ref-vol">269</span>:131–140.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11376945" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11376945</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="ml090.r3">Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD. Cell transformation by the superoxide-generating oxidase Mox1. <span><span class="ref-journal">Nature. </span>1999;<span class="ref-vol">401</span>:79–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10485709" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10485709</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="ml090.r4">Szanto I, Rubbia-Brandt L, Kiss P, Steger K, Banfi B, Kovari E, Herrmann F, Hadengue A, Krause KH. Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease. <span><span class="ref-journal">J Pathol. </span>2005;<span class="ref-vol">207</span>:164–176.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16086438" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16086438</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="ml090.r5">Rokutan K, Kawahara T, Kuwano Y, Tominaga K, Nishida K, Teshima-Kondo S. Nox enzymes and oxidative stress in the immunopathology of the gastrointestinal tract. <span><span class="ref-journal">Semin Immunopathol. </span>2008;<span class="ref-vol">30</span>:315–327.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18521607" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18521607</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="ml090.r6">Lim SD, Sun C, Lambeth JD, Marshall F, Amin M, Chung L, Petros JA, Arnold RS. Increased Nox1 and hydrogen peroxide in prostate cancer. <span><span class="ref-journal">Prostate. </span>2005;<span class="ref-vol">62</span>:200–207.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15389790" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15389790</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="ml090.r7">Arnold RS, Shi J, Murad E, Whalen AM, Sun CQ, Polavarapu R, Parthasarathy S, Petros JA, Lambeth JD. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2001;<span class="ref-vol">98</span>:5550–5555.</span> [<a href="/pmc/articles/PMC33250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC33250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11331784" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11331784</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="ml090.r8">Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. <span><span class="ref-journal">Cancer Lett. </span>2008;<span class="ref-vol">266</span>:37–52.</span> [<a href="/pmc/articles/PMC2673114/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2673114</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18406051" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18406051</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="ml090.r9">Kobayashi S, Nojima Y, Shibuya M, Maru Y. Nox1 regulates apoptosis and potentially stimulates branching morphogenesis in sinusoidal endothelial cells. <span><span class="ref-journal">Exp Cell Res. </span>2004;<span class="ref-vol">300</span>:455–462.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15475009" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15475009</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="ml090.r10">Jaquet V, Scapozza L, Clark R, Krause KH, Lambeth JD. Small Molecule NOX Inhibitors: ROS-generating NADPH Oxidases as Therapeutic Targets. <span><span class="ref-journal">Antioxidants & redox signaling. </span>2009</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19309261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19309261</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="ml090.r11">Cheng A, Merz KM Jr. Prediction of aqueous solubility of a diverse set of compounds using quantitative structure-property relationships. <span><span class="ref-journal">Journal of medicinal chemistry. </span>2003;<span class="ref-vol">46</span>:3572–3580.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12904062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12904062</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="ml090.r12">Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. Estimation of aqueous solubility of chemical compounds using E-state indices. <span><span class="ref-journal">Journal of chemical information and computer sciences. </span>2001;<span class="ref-vol">41</span>:1488–1493.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11749573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11749573</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="ml090.r13">Egan WJ, Merz KM Jr, Baldwin JJ. Prediction of drug absorption using multivariate statistics. <span><span class="ref-journal">Journal of medicinal chemistry. </span>2000;<span class="ref-vol">43</span>:3867–3877.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11052792" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11052792</span></a>]</div></dd><dt>14.</dt><dd><div class="bk_ref" id="ml090.r14">Egan WJ, Lauri G. Prediction of intestinal permeability. <span><span class="ref-journal">Advanced drug delivery reviews. </span>2002;<span class="ref-vol">54</span>:273–289.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11922948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11922948</span></a>]</div></dd><dt>15.</dt><dd><div class="bk_ref" id="ml090.r15">Aldieri E, Riganti C, Polimeni M, Gazzano E, Lussiana C, Campia I, Ghigo D. Classical inhibitors of NOX NAD(P)H oxidases are not specific. <span><span class="ref-journal">Current drug metabolism. </span>2008;<span class="ref-vol">9</span>:686–696.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18855607" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18855607</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
|
||
<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK47342</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/21433358" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">21433358</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml095/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml089/" title="Next page in this title">Next ></a></div></div></div></div>
|
||
|
||
</div>
|
||
|
||
<!-- Custom content below content -->
|
||
<div class="col4">
|
||
|
||
</div>
|
||
|
||
|
||
<!-- Book content -->
|
||
|
||
<!-- Custom contetnt below bottom nav -->
|
||
<div class="col5">
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div id="rightcolumn" class="four_col col last">
|
||
<!-- Custom content above discovery portlets -->
|
||
<div class="col6">
|
||
<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK47342&db=books">Share</a></div>
|
||
|
||
</div>
|
||
<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK47342/?report=reader">PubReader</a></li><li><a href="/books/NBK47342/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK47342" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK47342" style="display:none" title="Cite this Page"><div class="bk_tt">Brown SJ, Gianni D, Bokoch G, et al. Probe Report for NOX1 Inhibitors. 2009 Apr 23 [Updated 2010 Sep 2]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK47342/pdf/Bookshelf_NBK47342.pdf">PDF version of this page</a> (116K)</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#ml090.s2" ref="log$=inpage&link_id=inpage">Probe Structure & Characteristics</a></li><li><a href="#ml090.s3" ref="log$=inpage&link_id=inpage">Recommendations for the scientific use of this probe</a></li><li><a href="#ml090.s4" ref="log$=inpage&link_id=inpage">Scientific Rationale for Project</a></li><li><a href="#ml090.s5" ref="log$=inpage&link_id=inpage">Project Description</a></li><li><a href="#ml090.s13" ref="log$=inpage&link_id=inpage">Probe</a></li><li><a href="#ml090.s23" ref="log$=inpage&link_id=inpage">Appendices</a></li><li><a href="#ml090.s25" ref="log$=inpage&link_id=inpage">Bibliography</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=2358652" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcassay&DbFrom=books&Cmd=Link&LinkName=books_pcassay_probe&IdsFromResult=2358652" ref="log$=recordlinks">PubChem BioAssay for Chemical Probe</a><div class="brieflinkpop offscreen_noflow">PubChem BioAssay records reporting screening data for the development of the chemical probe(s) described in this book chapter</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcsubstance&DbFrom=books&Cmd=Link&LinkName=books_pcsubstance&IdsFromResult=2358652" ref="log$=recordlinks">PubChem Substance</a><div class="brieflinkpop offscreen_noflow">Related PubChem Substances</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=2358652" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/22834042" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimization and Characterization of an Inhibitor for NADPH Oxidase 1 (NOX-1).</a><span class="source">[Probe Reports from the NIH Mol...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimization and Characterization of an Inhibitor for NADPH Oxidase 1 (NOX-1).<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Gianni D, Nicolas N, Zhang H, Der Mardirossian C, Kister J, Martinez L, Ferguson J, Roush WR, Brown SJ, Bokoch GM, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Probe Reports from the NIH Molecular Libraries Program. 2010</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/29269607" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">Identification and Characterization of a Novel NADPH Oxidase 1 (Nox1) Inhibitor That Suppresses Proliferation of Colon and Stomach Cancer Cells.</a><span class="source">[Biol Pharm Bull. 2018]</span><div class="brieflinkpop offscreen_noflow">Identification and Characterization of a Novel NADPH Oxidase 1 (Nox1) Inhibitor That Suppresses Proliferation of Colon and Stomach Cancer Cells.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Yamamoto T, Nakano H, Shiomi K, Wanibuchi K, Masui H, Takahashi T, Urano Y, Kamata T. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Biol Pharm Bull. 2018 Mar 1; 41(3):419-426. Epub 2017 Dec 22.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20715845" ref="ordinalpos=1&linkpos=3&log$=relatedarticles&logdbfrom=pubmed">A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells.</a><span class="source">[ACS Chem Biol. 2010]</span><div class="brieflinkpop offscreen_noflow">A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Gianni D, Taulet N, Zhang H, DerMardirossian C, Kister J, Martinez L, Roush WR, Brown SJ, Bokoch GM, Rosen H. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">ACS Chem Biol. 2010 Oct 15; 5(10):981-93. </em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/27743884" ref="ordinalpos=1&linkpos=4&log$=relatedarticles&logdbfrom=pubmed">Peptide screen identifies a new NADPH oxidase inhibitor: impact on cell migration and invasion.</a><span class="source">[Eur J Pharmacol. 2017]</span><div class="brieflinkpop offscreen_noflow">Peptide screen identifies a new NADPH oxidase inhibitor: impact on cell migration and invasion.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Mousslim M, Pagano A, Andreotti N, Garrouste F, Thuault S, Peyrot V, Parat F, Luis J, Culcasi M, Thétiot-Laurent S, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Eur J Pharmacol. 2017 Jan 5; 794:162-172. Epub 2016 Oct 12.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/27476665" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Functional Heterogeneity of Nadph Oxidases in Atherosclerotic and Aneurysmal Diseases.</a><span class="source">[J Atheroscler Thromb. 2017]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Functional Heterogeneity of Nadph Oxidases in Atherosclerotic and Aneurysmal Diseases.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Kigawa Y, Miyazaki T, Lei XF, Kim-Kaneyama JR, Miyazaki A. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Atheroscler Thromb. 2017 Jan 1; 24(1):1-13. Epub 2016 Jul 29.</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=21433358" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=21433358" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d66c2e84f3725e592e20a6">Probe Report for NOX1 Inhibitors - Probe Reports from the NIH Molecular Librarie...</a><div class="ralinkpop offscreen_noflow">Probe Report for NOX1 Inhibitors - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d66c2d84f3725e592e1c53">Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2 - Probe Re...</a><div class="ralinkpop offscreen_noflow">Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2 - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d66c2c2f30673f7bf939be">Therapeutic Inhibitors of Phosphomannose Isomerase - Probe 2 - Probe Reports fro...</a><div class="ralinkpop offscreen_noflow">Therapeutic Inhibitors of Phosphomannose Isomerase - Probe 2 - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d66c2a84f3725e592e13e2">Three small molecule pan activator families of Ras-related GTPases - Probe Repor...</a><div class="ralinkpop offscreen_noflow">Three small molecule pan activator families of Ras-related GTPases - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d66c2967c23b31e0b3f051">uHTS for the identification of compounds that potentiate TRAIL-induced apoptosis...</a><div class="ralinkpop offscreen_noflow">uHTS for the identification of compounds that potentiate TRAIL-induced apoptosis of cancer cells - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
|
||
|
||
<!-- Custom content below discovery portlets -->
|
||
<div class="col7">
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<!-- Custom content after all -->
|
||
<div class="col8">
|
||
|
||
</div>
|
||
<div class="col9">
|
||
|
||
</div>
|
||
|
||
<script type="text/javascript" src="/corehtml/pmc/js/jquery.scrollTo-1.4.2.js"></script>
|
||
<script type="text/javascript">
|
||
(function($){
|
||
$('.skiplink').each(function(i, item){
|
||
var href = $($(item).attr('href'));
|
||
href.attr('tabindex', '-1').addClass('skiptarget'); // ensure the target can receive focus
|
||
$(item).on('click', function(event){
|
||
event.preventDefault();
|
||
$.scrollTo(href, 0, {
|
||
onAfter: function(){
|
||
href.focus();
|
||
}
|
||
});
|
||
});
|
||
});
|
||
})(jQuery);
|
||
</script>
|
||
</div>
|
||
<div class="bottom">
|
||
|
||
<div id="NCBIFooter_dynamic">
|
||
<!--<component id="Breadcrumbs" label="breadcrumbs"/>
|
||
<component id="Breadcrumbs" label="helpdesk"/>-->
|
||
|
||
</div>
|
||
|
||
<div class="footer" id="footer">
|
||
<section class="icon-section">
|
||
<div id="icon-section-header" class="icon-section_header">Follow NCBI</div>
|
||
<div class="grid-container container">
|
||
<div class="icon-section_container">
|
||
<a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11 {
|
||
fill: #737373;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>Twitter</title>
|
||
<path class="cls-11" d="M250.11,105.48c-7,3.14-13,3.25-19.27.14,8.12-4.86,8.49-8.27,11.43-17.46a78.8,78.8,0,0,1-25,9.55,39.35,39.35,0,0,0-67,35.85,111.6,111.6,0,0,1-81-41.08A39.37,39.37,0,0,0,81.47,145a39.08,39.08,0,0,1-17.8-4.92c0,.17,0,.33,0,.5a39.32,39.32,0,0,0,31.53,38.54,39.26,39.26,0,0,1-17.75.68,39.37,39.37,0,0,0,36.72,27.3A79.07,79.07,0,0,1,56,223.34,111.31,111.31,0,0,0,116.22,241c72.3,0,111.83-59.9,111.83-111.84,0-1.71,0-3.4-.1-5.09C235.62,118.54,244.84,113.37,250.11,105.48Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>Facebook</title>
|
||
<path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>LinkedIn</title>
|
||
<path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11,
|
||
.cls-12 {
|
||
fill: #737373;
|
||
}
|
||
|
||
.cls-11 {
|
||
fill-rule: evenodd;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>GitHub</title>
|
||
<path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z">
|
||
</path>
|
||
<path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1">
|
||
</path>
|
||
<path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08">
|
||
</path>
|
||
<path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path>
|
||
<path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog">
|
||
<svg xmlns="http://www.w3.org/2000/svg" id="Layer_1" data-name="Layer 1" viewBox="0 0 40 40">
|
||
<defs><style>.cls-1{fill:#737373;}</style></defs>
|
||
<title>NCBI Insights Blog</title>
|
||
<path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"></path>
|
||
</svg>
|
||
</a>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
|
||
<section class="container-fluid bg-primary">
|
||
<div class="container pt-5">
|
||
<div class="row mt-3">
|
||
<div class="col-lg-3 col-12">
|
||
<p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p>
|
||
<ul class="list-inline social_media">
|
||
<li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st20 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st30 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Twitter</title>
|
||
<g>
|
||
<g>
|
||
<g>
|
||
<path class="st20" d="M192.9,88.1c-5,2.2-9.2,2.3-13.6,0.1c5.7-3.4,6-5.8,8.1-12.3c-5.4,3.2-11.4,5.5-17.6,6.7 c-10.5-11.2-28.1-11.7-39.2-1.2c-7.2,6.8-10.2,16.9-8,26.5c-22.3-1.1-43.1-11.7-57.2-29C58,91.6,61.8,107.9,74,116 c-4.4-0.1-8.7-1.3-12.6-3.4c0,0.1,0,0.2,0,0.4c0,13.2,9.3,24.6,22.3,27.2c-4.1,1.1-8.4,1.3-12.5,0.5c3.6,11.3,14,19,25.9,19.3 c-11.6,9.1-26.4,13.2-41.1,11.5c12.7,8.1,27.4,12.5,42.5,12.5c51,0,78.9-42.2,78.9-78.9c0-1.2,0-2.4-0.1-3.6 C182.7,97.4,189.2,93.7,192.9,88.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st30" cx="124.4" cy="128.8" r="108.2"></circle>
|
||
</g>
|
||
</svg></a></li>
|
||
<li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank">
|
||
<svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st10 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st110 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Facebook</title>
|
||
<g>
|
||
<g>
|
||
<path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle>
|
||
</svg>
|
||
</a></li>
|
||
<li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<title>Youtube</title>
|
||
<style type="text/css">
|
||
.st4 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
|
||
.st5 {
|
||
fill: #FFFFFF;
|
||
}
|
||
</style>
|
||
<circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle>
|
||
<g transform="translate(0,-952.36218)">
|
||
<path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path>
|
||
</g>
|
||
</svg></a></li>
|
||
</ul>
|
||
</div>
|
||
<div class="col-lg-3 col-12">
|
||
<p class="address_footer text-white">National Library of Medicine<br />
|
||
<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
|
||
Bethesda, MD 20894</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
|
||
<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
|
||
<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
|
||
<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
|
||
<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
|
||
</div>
|
||
</div>
|
||
<div class="row">
|
||
<div class="col-lg-12 centered-lg">
|
||
<nav class="bottom-links">
|
||
<ul class="mt-3">
|
||
<li>
|
||
<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.nih.gov/">NIH</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.hhs.gov/">HHS</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
|
||
</li>
|
||
</ul>
|
||
</nav>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentOmnitureBaseJS/InstrumentNCBIConfigJS/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js?v=1"> </script>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/static/js/hfjs2.js"> </script>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<!--/.page-->
|
||
</div>
|
||
<!--/.wrap-->
|
||
</div><!-- /.twelve_col -->
|
||
</div>
|
||
<!-- /.grid -->
|
||
|
||
<span class="PAFAppResources"></span>
|
||
|
||
<!-- BESelector tab -->
|
||
|
||
|
||
|
||
<noscript><img alt="statistics" src="/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK47342&ncbi_domain=mlprobe&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK47342/&ncbi_pagename=Probe Report for NOX1 Inhibitors - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf" /></noscript>
|
||
|
||
|
||
<!-- usually for JS scripts at page bottom -->
|
||
<!--<component id="PageFixtures" label="styles"></component>-->
|
||
|
||
|
||
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal106 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
||
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
||
|
||
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3879255/4121861/3501987/4008961/3893018/3821238/4062932/4209313/4212053/4076480/3921943/3400083/3426610.js" snapshot="books"></script></body>
|
||
</html> |